Patients with severe mental illness (SMI) die younger than persons in the general population. Much of the excess mortality for SMI patients is attributable to cardiovascular disease, and is exacerbated by treatment with second-generation antipsychotics (2GAs). Although the cardiovascular risks are well-known, and safe, efficacious therapy exists, few SMI patients receive cardiovascular prevention drugs. Care delivery fragmentation and poor patient adherence are central problems to reducing cardiovascular risks for patients with SMI. To address these problems, we propose to conduct a multi-site, open-label, randomized controlled trial comparing an initial treatment strategy of free, fixed-doses of two generic, cardiovascular prevention drugs (statins and angiotensin drugs) delivered within mental health clinics versus usual treatment. The study will include 600 adult patients (18+ years old; 300 per arm) with schizophrenia, schizoaffective disorder, or bipolar disorder who are receiving 2GAs within four mental health clinics in the Boston area. We have three aims: 1) to compare the proportions of subjects in each arm who are receiving cardiovascular drug treatment and are adherent to therapy during 12-months of follow-up; 2) to compare changes in composite (e.g., Framingham scores) and individual (e.g., lipid levels) cardiovascular risk factor levels using an intent-to-treat (ITT) approach; and 3) to compare risk factor levels, accounting for variation in adherence over time, using causal inference techniques to estimate the per-protocol effect of the intervention. Thus, our three aims examine whether this low cost, streamlined treatment strategy increases the numbers of subjects receiving cardiovascular prevention therapy and improves cardiovascular risk levels. Because patient adherence is a major concern in this clinical area, we will supplement the ITT assessment of risk levels by using techniques such as marginal structural models with inverse probability weighting to account for time-varying adherence. We will follow subjects for up to 12 months, and collect interview and biometric data at baseline, 3-, 6-, 9-, and 12-months, and supplement these data with other sources of existing information, e.g., from electronic health records and the state All Payer Claims Database. This population-based initial treatment strategy could be an effective and efficient approach for overcoming traditional barriers to cardiovascular disease prevention within the SMI population. Findings from this study will inform efforts to improve care and outcomes, and to enhance survival for patients with severe mental illness.